Errors in erasure: Links between histone lysine methylation removal and disease

Elizabeth M. Duncan, C. David Allis

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

15 Scopus citations

Abstract

Many studies have demonstrated that covalent histone modifications are dynamically regulated to cause both chemical and physical changes to the chromatin template. Such changes in the chromatin template lead to biologically significant consequences, including differential gene expression. Histone lysine methylation, in particular, has been shown to correlate with gene expression both positively and negatively, depending on the specific site and degree (i.e., mono-, di-, or tri-) of methylation within the histone sequence. Although genetic alterations in the proteins that establish, or "write," methyl modifications and their effect in various human pathologies have been documented, connections between the misregulation of proteins that remove, or "erase," histone methylation and disease have emerged more recently. Here we discuss three mechanisms through which histone methylation can be removed from the chromatin template. We describe how these "erasure" mechanisms are linked to pathways that are known to be misregulated in diseases, such as cancer. We further describe how errors in the removal of histone methylation can and do lead to human pathologies, both directly and indirectly.

Original languageEnglish
Title of host publicationEpigenetics and Disease
Subtitle of host publicationPharmaceutical Opportunities
EditorsSusan Gasser, En Li
Pages69-90
Number of pages22
DOIs
StatePublished - 2011

Publication series

NameProgress in Drug Research
Volume67
ISSN (Print)0071-786X

Bibliographical note

Funding Information:
We would like to thank Gang Wang, Ping Chi, Joanna Wysocka, and Aaron Goldberg for a critical reading of the manuscript and for helpful advice in its preparation. We apologize to all those whose work we could not cite due to space constraints. C.D.A. is supported by NIH Grant GM53512, and both C.D.A. and E.M.D. are supported by a grant from the Tri-Institutional Stem Cell Initiative (funded by the Starr Foundation).

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics (all)

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